FDA Requires Lower Doses for Certain Insomnia Drugs

By

Jennifer Corbett Dooren

Updated Jan. 10, 2013 7:15 p.m. ET

WASHINGTON—The Food and Drug Administration is requiring the makers of certain sleep-inducing drugs, including Ambien, to lower doses of the medicines because they have been shown to impair activities—such as driving—the morning after the drugs have been taken.

The FDA said current recommended doses of Ambien and similar drugs should be cut in half for women and that the labeling should recommend doctors consider a lower dose for men.

ENLARGE

Tablets of Sanofi's Ambien CR
Bloomberg News

The new requirement applies to sleep-inducing drugs that contain the active ingredient zolpidem, which is found in drugs such as Ambien, Ambien CR, Edluar and Zolpimist. Sanofi SASNY0.78% markets Ambien, but the products are also available in generic versions, the FDA said.

In a statement, Sanofi said it has been in contact with the FDA about the new dosing recommendations and would continue talking to the agency. "Sanofi stands behind the significant clinical data demonstrating the safety and efficacy of Ambien, which was FDA approved in the U.S. in 1992," the company said.

The sleeping drugs are widely prescribed, with almost 40 million prescriptions written in the U.S. in 2011, according to information provider IMS Health.

The FDA said new data have shown that levels of the drugs in the blood of some patients—particularly women—may be high enough the morning after use to impair driving and other tasks that require alertness. Women eliminate zolpidem from their bodies more slowly than men.

Ambien and other drugs containing zolpidem are considered sedative-hypnotic drugs and are designed to treat insomnia by helping people fall and stay asleep. The drugs are meant for short-term use, although the exact length of treatment isn't defined in the drugs' labels.

The agency said doses for the immediate-release versions of zolpidem for women should be lowered to five milligrams from 10 milligrams. The extended-release versions—or Ambien CR—should be cut to 6.25 milligrams from 12.5 milligrams. The FDA said doctors should consider putting patients on the lowest possible dose for all types of sleep-inducing medicines. Doctors usually follow the FDA's recommendations on the use of drugs.

Ellis Unger, a director in the FDA's drug division, said the risks of things such as car accidents are highest for patients taking the extended-release versions of Ambien and generics because the products are designed to stay in the bloodstream longer. Immediate-release versions include regular Ambien and generics, along with Edluar, a tablet placed under the tongue and sold by a unit of MedaMEDAA0.36% AB, as well as Zolpimist, an oral spray marketed by a Hi-Tech Pharmacal Co. subsidiary.

Dr. Unger said patients who are currently taking the higher doses of the drugs shouldn't make any adjustments on their own and should talk to their doctors.

The dosage reductions aren't being required for a drug called Intermezzo, a zolpidem-containing drug meant to counter middle-of-the-night waking, because it was approved in November 2011 with lower doses for women. Intermezzo is marketed by Transcept Pharmaceuticals Inc. and Purdue Pharma LP.

Although the FDA has received reports for years about car crashes possibly associated with sleep-inducing drugs, it wasn't until recently that clinical data became available showing how some products could impair driving several hours after being taken.

Dr. Unger said some of the new clinical information came from driving tests that were conducted as part of the development program for Intermezzo. The FDA combined those data with other blood-level data from other drug makers to show that some people kept high levels of the medications in their blood for more than eight hours after taking the drugs.

Patients who are taking Ambien and similar drugs are instructed to take it only if they plan to get a full night's sleep of seven to eight hours.

The FDA said it has received more than 700 reports involving zolpidem and impaired driving, with an increase in 2007 after the FDA updated drug labels to warn of sleep-driving, or patients getting out of bed and driving while they aren't fully awake. However, the reports alone aren't enough to link a drug with an accident, Dr. Unger said.

Dr. Unger said the FDA didn't have information about the role of other drugs, alcohol or the time when drugs were taken before the accident. He explained that the agency needed to wait for scientific evidence linking zolpidem and next-morning impairment affecting driving and other tasks.

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